Abstract
Malignant melanoma is the third most common type of tumor that causes brain metastases. Patients with cerebral involvement have a dismal prognosis and their treatment is an unmet medical need. Brain involvement is a multistep process involving several signaling pathways such as Janus kinase/signal Transducer and Activator of Transcription (JAK/STAT), Phosphoinositide 3-kinase/Protein Kinase B (PI3K/AKT), Vascular Endothelial Growth Factor and Phosphatase and Tensin Homolog (PTEN). Recently therapy that targets the MAPK signaling (BRAF/MEK inhibitors) and immunotherapy (anti-CTLA4 and anti-PD1 agents) have changed the therapeutic approaches to stage IV melanoma. In contrast, there are no solid data about patients with brain metastases, who are usually excluded from clinical trials. Retrospective data showed that BRAF-inhibitors, alone or in combination with MEK-inhibitors have interesting clinical activity in this setting. Prospective data about the combinations of BRAF/MEK inhibitors have been recently published, showing an improved overall response rate. Short intracranial disease control is still a challenge. Several attempts have been made in order to improve it with combinations between local and systemic therapies. Immunotherapy approaches seem to retain promising activity in the treatment of melanoma brain metastasis as showed by the results of clinical trials investigating the combination of anti-CTL4 (Ipilimumab) and anti-PD1(Nivolumab). Studies about the combination or the sequential approach of target therapy and immunotherapy are ongoing, with immature results. Several clinical trials are ongoing trying to explore new approaches in order to overcome tumor resistance. At this moment the correct therapeutic choices for melanoma with intracranial involvement is still a challenge and new strategies are needed.
Highlights
Melanoma, following breast and lung cancer, is the third most common type of cancer that metastasizes to the central nervous system (CNS)
The results of this study suggest that intracranial responses in patients with BRAFV600 mutated melanoma were improved by the association of Dabrafenib and Trametinib, compared with the single-agent treatment
Patients with metastatic melanoma with CNS involvement still have a worse prognosis compared with patients with the extracranial disease
Summary
Melanoma, following breast and lung cancer, is the third most common type of cancer that metastasizes to the central nervous system (CNS). Overall survival (OS) of patients with stage IV melanoma has been significantly improved and the median OS can reach up to 23 months [7]. Both forms of therapy have a potential impact on the disease when it has spread to the brain [8]. We review data about the impact of target therapies, in combination with radiotherapy, chemotherapy, and immunotherapy, in the populations of patients with stage IV melanoma with brain and leptomeningeal disease, and, last we summarize some new approaches which are still under investigation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
